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Upregulation Of Mxi1-0 By FOXO3a Promotes Apoptosis Of Endothelial Cells After Hypoxia

Posted on:2020-07-14Degree:MasterType:Thesis
Country:ChinaCandidate:Z WuFull Text:PDF
GTID:2370330596984084Subject:Academy of Pediatrics
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ObjectiveIn this study,we established a human umbilical vein endothelial cell(HUVEC)hypoxia model to investigate the potential mechanism between hypoxia-induced endothelial cell apoptosis and vascular disease,and to investigate the expression of Mxi1-0 and the role of apoptosis induced by HIF-1? and FOXO3 a in HUVEC hypoxia model.MethodsHUVEC was treated with hypoxia,and small interfering RNA(siRNA)was transfected to silence the expression of HIF-1?(siHIF-1?)and FOXO3(siFOXO3).The cell viability was detected by CCK-8,the apoptosis of HUVEC was detected by TUNEL method,the protein expression levels of HIF-1?,FoxO3 a and Mxi1-0 were detected by Western blot,the mRNA level of Mxi1-0 was detected by RT-PCR.The subcellular localization of FoxO3 a was detected by immunofluorescence,and the enrichment of HIF-1? and FoxO3 a in the Mxi1-0 promoter region was analyzed by ChIP.ResultsIn the present study,we first found that hypoxia stimulation up-regulated Mxi1-0 expression and triggered apoptosis in HUVECs.In addition,hypoxia stimulation induced activation of FOXO3,while transfection of siFOXO3 inhibited hypoxia-induced Mxi1-0 expression and HUVEC apoptosis.Using the ChIP assay,we confirmed that FOXO3 a can bind to the promoter region of Mxi1-0.Finally,we found that transfection of siHIF-1? inhibits hypoxia-induced HIF-1? expression and activation of FOXO3 a / Mxi1-0 axis and apoptosis of HUVEC cells.In conclusion,this study elucidated the signaling pathway of HIF-1?/FOXO3 a / Mxi1-0 in hypoxia-induced HUVEC apoptosis.These data also indicate that HIF-1? is required for FOXO3 a to mediate Mxi1-0 upregulation and apoptosis in the HUVEC hypoxia model.ConclusionHypoxia stimulation induces binding of FOXO3 a to the Mxi1-0 promoter.Hypoxia stimulation triggers HIF-1?-dependent FOXO3a-mediated upregulation of Mxi1-0 and apoptosis of HUVEC cells.
Keywords/Search Tags:Mxi1-0, FOXO3a, HIF-1?, Hypoxia, Apoptosis, Endothelial Cells
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